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Open AccessFeature PaperArticle

Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients

1
Department of Gynecology and Obstetrics, University Hospital of Essen, 45122 Essen, Germany
2
QIAGEN GmbH, 40724 Hilden, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Françoise Farace
Cells 2021, 10(2), 212; https://doi.org/10.3390/cells10020212
Received: 14 December 2020 / Revised: 8 January 2021 / Accepted: 18 January 2021 / Published: 21 January 2021
(This article belongs to the Special Issue Liquid Biopsy)
Dynamics of mRNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) were assessed to examine the relevance of a longitudinal multi-parametric liquid biopsy strategy. Eighteen milliliters of blood was drawn from 27 hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients at disease progression and at two subsequent radiologic staging time points. CTC mRNA and EV mRNA were analyzed using multi-marker qPCR, and cfDNA was analyzed using targeted next-generation sequencing (NGS). The presence of ERBB2 or ERBB3 overexpression signals in CTCs significantly correlated with disease progression (87% specificity, 36% sensitivity, p-value = 0.023), and the presence of either ERBB3 signals in CTCs or EVs or cfDNA variants in ERBB3 also showed a significant association with progressive MBC. Fluctuations during treatment were detected in the EV fraction with the appearance of hitherto undetected ERCC1 signals correlating with progressive disease (97% specificity, 18% sensitivity, p-value = 0.030). Allele frequency development of ESR1 and PIK3CA variants detected at subsequent staging time points could be used as a predictor for therapy success and, importantly, might help guide therapy decisions. The three analytes, each with their own unique features for disease monitoring, were shown to be complementary, underlining the usefulness of the longitudinal multi-parametric liquid biopsy approach. View Full-Text
Keywords: multi-parametric; multi-modal; multi-analyte; follow-up; serial sampling; gene expression; molecular signature; mutation; next-generation sequencing; unique molecular indices multi-parametric; multi-modal; multi-analyte; follow-up; serial sampling; gene expression; molecular signature; mutation; next-generation sequencing; unique molecular indices
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MDPI and ACS Style

Keup, C.; Suryaprakash, V.; Storbeck, M.; Hoffmann, O.; Kimmig, R.; Kasimir-Bauer, S. Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients. Cells 2021, 10, 212. https://doi.org/10.3390/cells10020212

AMA Style

Keup C, Suryaprakash V, Storbeck M, Hoffmann O, Kimmig R, Kasimir-Bauer S. Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients. Cells. 2021; 10(2):212. https://doi.org/10.3390/cells10020212

Chicago/Turabian Style

Keup, Corinna; Suryaprakash, Vinay; Storbeck, Markus; Hoffmann, Oliver; Kimmig, Rainer; Kasimir-Bauer, Sabine. 2021. "Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients" Cells 10, no. 2: 212. https://doi.org/10.3390/cells10020212

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